This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Using Molecular Dynamic (MD) simulations and computational protein modification, we will characterize PDZ-ligand complexes of the Na/H Exchange Regulatory Factor-1 (NHERF1) due to their biological and medicinal importance. We will investigate the PDZ1/PDZ2-ligand interactions. To probe such interactions we will use the five amino acid residue carboxy-terminal recognition motifs from the NaPi cotransporter (NATRL;L1), PTH receptor (WETVM;L2) or NHERF1(LFSNL;L3). We will estimate the binding affinity of PDZ1 for both L1 and L2 and PDZ2 for L2 and L3. By combining molecular modeling of isolated PDZ domains, a model for tandem PDZ1-PDZ2 will be proposed.